An efficient and high yield method for the N-tert-butoxycarbonyl protection of sterically hindered amino acids

Khalil, Ehab M.; Subasinghe, Nalin L.; Johnson, Rodney L.

doi:10.1016/0040-4039(96)00589-8

Cited by 59 publications

(41 citation statements)

References 11 publications

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“…Treatment of the commercially available amino acid with acrylonitrile under basic conditions (NaOH, H 2 O, 4-22 8C, 16 h) followed by Boc-protection of the sterically hindered secondary amine ([(CH 3 ) 4 NOH]·5 H 2 O, Boc 2 O, CH 3 CN, 22 8C, 3 days) gave the corresponding intermediates 5 a and 5 b. [14] Following esterification, hydride induced ring closing of the cyano ester, and subsequent treatment of the b keto nitrile (7 a and 7 b) with hydrazine in the presence of acetic acid provided the desired core structure (8 a and 8 b). These scaffolds were protected on the pyrazole ring using ethyl chloroformate.…”

Section: Chemistrymentioning

confidence: 99%

6‐Substituted Pyrrolo[3,4‐c]pyrazoles: An Improved Class of CDK2 Inhibitors

Brasca

Albanese

Amici³

et al. 2007

ChemMedChem

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We have recently reported a new class of CDK2/cyclin A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. The introduction of small alkyl or cycloalkyl groups in position 6 of this scaffold allowed variation at the other two diversity points. Conventional and polymer-assisted solution phase chemistry provided a way of generating compounds with improved biochemical and cellular activity. Optimization of the physical properties and pharmacokinetic profile led to a compound which exhibited good efficacy in vivo on A2780 human ovarian carcinoma.

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Section: Chemistrymentioning

confidence: 99%

6‐Substituted Pyrrolo[3,4‐c]pyrazoles: An Improved Class of CDK2 Inhibitors

Brasca

Albanese

Amici³

et al. 2007

ChemMedChem

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“…These difficulties can be overcome by working in a polar aprotic solvent with a lipophilic base (tetramethylammonium hydroxide, TMAH), which enhances the amino acid salt's solubility in the organic solvent. [36] This methodology (TMAH, acetonitrile, Boc 2 O) was used in several different attempts to protect the amino group of trans-c 6 Phe. The solubility of the starting material proved to be critical for the reaction yield: when the tetramethylammonium salt was not completely dissolved, the reaction proceeded very slowly and gave a very poor yield.…”

Section: Synthesis Of Racemic Trans-c 6 Phementioning

confidence: 99%

Synthesis and Preparative Resolution of the trans‐Cyclohexane Analogues of Phenylalanine

2004

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Different approaches to the synthesis of enantiomerically pure (1R,2S)‐ and (1S,2R)‐1‐amino‐2‐phenylcyclohexanecarboxylic acids (trans‐c6Phe) through a racemic pathway followed by semi‐preparative HPLC of a racemic precursor have been studied. The complete diastereoselectivity of the Strecker reaction and the high efficiency of the subsequent transformations into the amino acid favour this method in comparison to the Diels−Alder route. The relative stereochemistry of the amino acid and its precursors has been unambiguously assigned. The preparation of the final enantiomerically pure amino acids and their corresponding N‐Boc derivatives was carried out by HPLC resolution of one of the intermediates using a cellulose‐derived chiral stationary phase. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

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“…The synthesis of racemic (hMe)Aoc and the gas chromatographic separation of selected diastereomeric esters at the analytical level have already been published [25]. The Z-protected derivative was prepared by reacting the free amino acid with N-(benzyloxycarbonyl)-succinimide in MeCN in the presence of the lipophilic base tetramethylammonium hydroxide [26]. Gly and Aib tert-butyl esters were obtained by esterification of the corresponding Z-protected amino acid with isobutylene in the presence of a catalytic amount of sulphuric acid [27].…”

Section: Peptide Synthesismentioning

confidence: 99%

Preferred solution conformation of peptides rich in the lipophilic, chiral, Cα-methylated α-amino acid (αMe)Aoc

et al. 1999

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The lipophilic, chiral, C(alpha)-methylated alpha-amino acid L-(alphaMe)Aoc (2-methyl-2-amino-octanoic acid) was prepared using a chemo-enzymatic approach. Two series of terminally protected model peptides, from dimer through to hexamer, containing L-(alphaMe)Aoc in combination with either Gly or Aib, were synthesized by solution methods and were fully characterized. A solution conformational analysis, based on FT-IR absorption, 1H-NMR and circular dichroism (CD) techniques, was performed with the aim at determining the preferred conformation of this novel amino acid and the relationship between chirality at its alpha-carbon atom and screw sense of the helix that is formed. The results obtained strongly support the view that L-(alphaMe)Aoc favours the formation of the right-handed 3(10)-helical conformation.

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An efficient and high yield method for the N-tert-butoxycarbonyl protection of sterically hindered amino acids

Cited by 59 publications

References 11 publications

6‐Substituted Pyrrolo[3,4‐c]pyrazoles: An Improved Class of CDK2 Inhibitors

6‐Substituted Pyrrolo[3,4‐c]pyrazoles: An Improved Class of CDK2 Inhibitors

Synthesis and Preparative Resolution of the trans‐Cyclohexane Analogues of Phenylalanine

Preferred solution conformation of peptides rich in the lipophilic, chiral, Cα-methylated α-amino acid (αMe)Aoc

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